P672: REAL-LIFE EFFICACY AND SAFETY OF VENETOCLAX MONOTHERAPY IN RELAPSED/ REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA - INTERIM ANALYSIS OF MULTICENTRIC STUDY VERONE
Authors: L. Ysebaert, X. Troussard, V. Levy, R. Le Calloch, R. Guieze, S. Leprêtre, A.-S. Michallet, V. Leblond, P. Feugier, J. Ramier, A. Delmer
Journal: HemaSphere (2022)

Background: The efficacy and safety of venetoclax (VEN), the first oral inhibitor of BCL-2, has been demonstrated in clinical trials in patients with chronic lymphocytic leukemia (CLL). However, few real-life data in France is available today on this treatment. Aims: VERONE is an observational ongoing study, it aims to describe the efficacy and tolerance of VEN in a real-life situation, as well as its use in current medical practice. Methods: This longitudinal non-interventional study is conducted in adults starting treatment with VEN for CLL, with a follow-up over 48 months. This second interim analysis was performed in patients treated with monotherapy until progression, 43 months after the first inclusion. The overall response rate (ORR, assessed by investigator) and progression-free survival (PFS) were estimated 1 and 2 years after the first intake of VEN in patients with at least one follow-up visit in the study (evaluable population). Results: From March 2018 to September 2021, 196 patients included in 64 centers started VEN as monotherapy for CLL (tolerance population), 195 met the selection criteria (analysis population) and 113 could be evaluated (evaluable population). In the analysis population (n = 195), patients and CLL characteristics at baseline were: median age 74.0 years (33.0-91.0), male 68.2%, ECOG ≥2 18.5%, ≥1 comorbidities 87.7%, median time since diagnosis 8.3 years (0.0-29.4), 37.3% of 169 genetic examinations was TP53 and/ or del (17)p, median number of previous treatments 2 (1-9) (chemoimmunotherapy 87.2%, BCR inhibitors (ibrutinib, idelalisib) 70.8%). Before the first intake of VEN, preventive measures against tumor lysis syndrome (TLS) were taken in the majority of cases (hospitalization 85.2%, hydration 85.2% and anti-hyperuricemia prophylaxis 66.3%). The median duration of the titration period was 5.0 weeks, and 77.0% of patients reached the recommended dose of 400mg at the time of analysis. In the 113 evaluable patients, the overall response rate was 91.2% [95%CI 84.5%-95.1%] at 1 year and 92.9% [95%CI 86.7%-96.4%] at 2 years. After a median follow-up of 23.2 months, the PFS rate was 81.8% [95%CI 72.5%-88.2%] at 1 year and 71.1% [95%CI 58.0% 80.7%] at 2 years. The median duration of treatment was 15.5 months. In terms of safety, 85.2% of the 196 patients presented adverse events [AEs, neutropenia (46.4%) and diarrhea (24.5%)], including 64.3% of AEs of grade ≥3 (including 32.7% neutropenia). Permanent discontinuation of treatment due to AEs related to VEN was observed in 20.4% of patients. 4 AEs grade 5 related to VEN was observed in 3 patients (deterioration of general condition, ascites, hepatic failure, death). At inclusion, the risk level of developing TLS, assessed in 149 patients, was low (28.2%) moderate (69.8%) or high (2.0%). During the dose escalation phase, 19 patients (9.7%) developed TLS and 4 (2.0%) stopped VEN treatment. Summary/Conclusion: This real-life study confirms the efficacy of VEN in heavily treated patients with a safety profile little different from that observed in selected populations in clinical trials.